Chemically modified silicas are widely used as packing supports in chromatographic separations for the purification of water soluble products. Generally, modified silica packings comprise derivatized silicas to which organic substituents, such as alkyl chains, have been attached. Those packings can deteriorate and release silica as a contaminant into purified products as a result of chemical attack by the mobile phase. Problematic mobile phases include water, low molecular weight alcohols, and mobile phases having a pH outside the range of about 2 to about 7.
It has heretofore been accepted that the release of silica into purified products is an unavoidable consequence of the packing's ability to perform properly in chromatographic purification processes. In situations where silica content must be reduced to meet product specifications, such as for pharmaceutical compounds, ion exchange resins have been used to remove silica. See U.S. Pat. No. 5,204,005 to Doran, et al. However, soluble polymeric or colloidal silica removal by ion exchange chromatography is undesirable because resins must be regenerated, a process step that generates waste streams is added, operating costs are increased, and capital expenditure is required. In addition, ion exchange chromatography exposes the desired product to extremes of pH which may be undesirable for x-ray contrast media and is prohibited for MRI agents.
A need remains for processes for the efficient and cost effective removal of silica from water soluble products.